Impact of minocycline on cerebrospinal fluid markers of oxidative stress,
neuronal injury, and inflammation in HIV-seropositive individuals with cognitive
impairment.
Author(s): Sacktor N(1), Miyahara S, Evans S, Schifitto G, Cohen B, Haughey N, Drewes JL,
Graham D, Zink MC, Anderson C, Nath A, Pardo CA, McCarthy S, Hosey L, Clifford D;
ACTG A5235 team.
Affiliation(s): Author information:
(1)Johns Hopkins University School of Medicine, Baltimore, MD, USA,
sacktor@jhmi.edu.
Publication date & source: 2014, J Neurovirol. , 20(6):620-6
Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress,
neuronal injury, and inflammation and decreased neurotransmitter levels have been
reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have
a neuroprotective effect by inhibiting inducible nitric oxide synthase, which
produces nitric oxide, a compound that induces oxygen free radical production. In
A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of
Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline
was not associated with cognitive improvement, but the effect on the above CSF
measures was not examined previously. The objective of this study was to examine
the effect of minocycline on markers of oxidative stress, neuronal injury,
neurotransmitter levels, and inflammation from CSF in participants in A5235. One
hundred seven HIV+ individuals received either minocycline 100 mg or placebo
orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional
lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides
and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine
metabolites, neurofilament heavy chain, and inflammatory cytokines were measured
in the CSF before and after treatment. The 24-week change in ceramides was larger
in a beneficial direction in the minocycline group compared to the placebo group.
The two groups did not differ in the 24-week changes for other markers.These
results suggest that minocycline may decrease lipid markers of oxidative stress
(ceramides) in individuals with HAND; however, an effect of minocycline on other
CSF markers was not observed. A larger sample size is needed to further validate
these results.
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